Metabolic models have been proven to be useful tools in system biology and have been successfully applied to various research fields in a wide range of organisms. A relatively complete metabolic network is a prerequisite for deriving reliable metabolic models. The first step in constructing metabolic network is to harmonize compounds and reactions across different metabolic databases. However, effectively integrating data from various sources still remains a big challenge. Incomplete and inconsistent atomistic details in compound representations across databases is a very important limiting factor. Here, we optimized a subgraph isomorphism detection algorithm to validate generic compound pairs. Moreover, we defined a set of harmonization relationship types between compounds to deal with inconsistent chemical details while successfully capturing atom-level characteristics, enabling a more complete enabling compound harmonization across metabolic databases. In total, 15,704 compound pairs across KEGG (Kyoto Encyclopedia of Genes and Genomes) and MetaCyc databases were detected. Furthermore, utilizing the classification of compound pairs and EC (Enzyme Commission) numbers of reactions, we established hierarchical relationships between metabolic reactions, enabling the harmonization of 3856 reaction pairs. In addition, we created and used atom-specific identifiers to evaluate the consistency of atom mappings within and between harmonized reactions, detecting some consistency issues between the reaction and compound descriptions in these metabolic databases.

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Published in Metabolites, v. 11, issue 7, 431.

© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Funding Information

The work was supported by grant NSF 2020026 (PI Moseley).

Related Content

All data used and the results generated in the manuscript are available on: https://doi.org/10.6084/m9.figshare.14703999 accessed on 1 April 2021.

The following are available online at https://www.mdpi.com/article/10.3390/metabo11070431/s1, Figure S1: Reaction pair with mismatch of last EC number, Figure S2: Reaction pair with missing 4th-level EC number designation, Figure S3: Example of atoms with interchangeable mappings, Figure S4: Comparison of KEGG RCLASS and RPAIR description for compound pair C01255 and C02378, Table S1: Incorrect RDM descriptions, Table S2: Hardly interpretable compound pairs, Table S3: Harmonized reactions with inconsistent atom mappings. These materials are also available for download as the additional file listed at the end of this record.

metabolites-11-00431-s001.zip (711 kB)
Supplementary materials